Studies of the pathogenesis of visna in sheep have been focussed in two areas: 1) the mechanism of the persistent virus infection; 2) the mechanism of induction of the lesions in the central nervous system. Our proposed studies for the coming year are to continue and extend our investigation of antigenic shift of visna virus as the mechanism of persistence. Specifically, questions relating to the mechanism of origin and time of origin of mutant viruses in cell cultures as well as in sheep will be attempted. Further studies on the antigenic stability of the mutants will also be done with regard to mechanisms of pathologic effect of the infection, our preliminary findings of an acute induction of specifically sensitized lymphocytes in cerebrospinal fluid and blood of inoculated sheep offer a fruitful avenue for further study. These studies will be repeated and extended in the coming year.